E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent or metastatic cervical cancer |
|
E.1.1.1 | Medical condition in easily understood language |
recurrent or metastatic cervical cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008342 |
E.1.2 | Term | Cervix carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Determine the anti-tumor efficacy in patients with cervical cancer |
|
E.2.2 | Secondary objectives of the trial |
• Evaluate tumor response durability
• Evaluate clinical response
• Assess safety and tolerability
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with extra-pelvic metastatic or recurrent cervical cancer with
squamous cell, adenocarcinoma or adenosquamous histology, that:
1. Have experienced disease progression during or after treatment with:
- Paclitaxel+cisplatin or carboplatin OR
- Paclitaxel+topotecan,
in combination with bevacizumab unless patients are ineligible for
bevacizumab treatment according to local standards.
2. Have received no more than 2 prior systemic treatment regimens for
recurrent or metastatic cervical cancer. Chemotherapy administered in
the adjuvant or neoadjuvant setting, or in combination with radiation
therapy should not be counted as a prior systemic treatment regimen.
3. Are not candidates for curative therapy, including but not limited to,
radiotherapy or exenterative surgery.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
• Life expectancy of at least three months
• A negative serum pregnancy test for patients of reproductive potential
• Patients of reproductive potential must agree to use adequate
contraception during and for 6 months after the last IMP administration
• Following receipt of verbal and written information about the trial,
patients must provide signed informed consent before any trial-related
activity is carried out
• Acceptable coagulation status:
- For patients not on anti-coagulation therapy:
o Activated partial thromboplastin time (aPTT) ≤ 1.25 ULN.
o International normalized ratio (INR) ≤ 1.2.
- For patients on anti-coagulation therapy:
o aPTT ≤ 1.25 ULN.
o INR:
*Patients on anti-coagulants that require laboratory
assessments for dose titration (warfarin or other Vitamin K dependent
anti-coagulant agents) must be on a steady dose (no active titration) for
4 weeks prior to first planned administration of tisotumab vedotin and
have an INR ≤ 2.5 for eligibility.
*Patients on anti-coagulants that do not require laboratory
assessments for dose titration do not to be on a steady dose for > 4
weeks prior to first planned administration of tisotumab vedotin.
o Concurrent chronic use of prophylactic AcetylSalicylic Acid (ASA,
e.g., aspirin) is prohibited on any type of anti-coagulation therapy. |
|
E.4 | Principal exclusion criteria |
• Known past or current coagulation defects
• Ongoing major bleeding
• Clinically significant cardiac disease
• Other cancer: Known past or current malignancy other than inclusion
diagnosis
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Confirmed objective response rate based upon RECIST v1.1 assessed by the independent review committee |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
|
E.5.2 | Secondary end point(s) |
• Duration of response (DOR) based upon RECIST v1.1
• Confirmed objective response rate based upon RECIST v1.1 assessed by the investigator
• Time to response based upon RECIST v1.1
• Progression free survival based upon RECIST v1.1
• Overall survival
• Adverse events and safety laboratory parameters
• Pharmacokinetics (PK)
• Immunogenicity
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czechia |
Denmark |
Germany |
Italy |
Spain |
Sweden |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |